Women fare poorer in Alzheimer's progression
Posted by on September 10, 2012 - 9:04am

New research shows that women with Alzheimer’s disease show worse mental deterioration than men, even when at the same stage of the the disease.

According to researchers at the University of Hertfordshire, men with Alzheimer’s consistently performed better than women across the five cognitive areas they examined.

Most remarkably, the verbal skills of women with Alzheimer’s are worse when compared to men with the disease.   This finding is a striking difference to the profile for the healthy population where females have a distinct advantage.

Led by Keith Laws, Ph.D., the research team completed a meta-analysis of neurocognitive data from 15 published studies, which revealed a consistent male advantage on verbal and visuospatial tasks, as well as on tests of both episodic memory and semantic memory.

Episodic memory describes our ability to recall specific events of our own past, accompanied by the feeling of remembering. Semantic memory is knowledge that we acquire that is purely factual without any personal feeling or history attached.

“Unlike mental decline associated with normal aging, something about Alzheimer’s specifically disadvantages women,” said Laws, a psychology professor.

The influence of hormones might be a possible explanation, he said, pointing to a loss of estrogen in women. Another theory is that men have a “greater cognitive reserve” that protects against the disease, he said.  Further analysis of the data showed that age, education level and dementia severity did not explain the advantage that men with the disease have over women, he added.

Alzheimer’s disease, a progressive condition affecting memory, thinking, behavior and emotion, is the most common form of dementia.

Alzheimer’s Disease International estimates that there are currently 30 million people in the world with dementia, with 4.6 million new cases every year. The incidence of Alzheimer’s is greater among women than men, with the difference increasing with age, researchers note.

The new study was published in the Journal of Clinical and Experimental Neuropsychology.

Source: University of Hertfordshire

Cracking the Genetic Code for Alzheimer's Disease
Posted by on March 21, 2011 - 8:59am

Scientists crack code to create neurons whose early death causes memory loss

Northwestern Medicine researchers for the first time have transformed a human embryonic stem cell into a critical type of neuron that dies early in Alzheimer’s disease and is a major cause of memory loss.  This new ability to reprogram stem cells and grow a limitless supply of the human neurons will enable a rapid wave of drug testing for Alzheimer’s disease, allow researchers to study why the neurons die and could potentially lead to transplanting the new neurons into people with Alzheimer’s.  The paper will be published March 4 in the journal Stem Cells.

These critical neurons help retrieve memories in the brain. In early Alzheimer’s, the ability to retrieve memories is lost, not the memories themselves. There is a relatively small population of these neurons in the brain, and their loss has a swift and devastating effect on the ability to remember.

“Now that we have learned how to make these cells, we can study them in a tissue culture dish and figure out what we can do to prevent them from dying,” said senior study author Jack Kessler, M.D., chair of neurology and the Davee Professor of Stem Cell Biology at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital. “This technique to produce the neurons allows for an almost infinite number of these cells to be grown in labs, allowing other scientists the ability to study why this one population of cells selectively dies in Alzheimer’s disease,” said Christopher Bissonnette, a former doctoral student in neurology who labored for six years in Kessler’s lab to crack the genetic code of the stem cells to produce the neurons. His research was motivated by his grandfather’s death from Alzheimer’s.

The ability to make the cells also means researchers can quickly test thousands of different drugs to see which ones may keep the cells alive when they are in a challenging environment. This rapid testing technique is called high-throughput screening.

Kessler and Bissonnette demonstrated the newly produced neurons work just like the originals. They transplanted the new neurons into the hippocampus of mice and showed the neurons functioned normally. The neurons produced axons, or connecting fibers, to the hippocampus and pumped out acetylcholine, a chemical needed by the hippocampus to retrieve memories from other parts of the brain.

Human Skin Cells Transformed into Stem Cells and then Neurons

In new, unpublished research, Northwestern Medicine scientists also have discovered a second novel way to make the neurons. They made human embryonic stem cells (called induced pluripotent stem cells) from human skin cells and then transformed these into the neurons.   Scientists made these stem cells and neurons from skin cells of three groups of people: Alzheimer’s patients, healthy patients with no family history of Alzheimer’s, and healthy patients with an increased likelihood of developing the disease due to a family history of Alzheimer’s because of genetic mutations or unknown reasons.

“This gives us a new way to study diseased human Alzheimer’s cells,” Kessler said. “These are real people with real disease. That’s why it’s exciting.”

by Marla Paul Northwestern health sciences editor.

Hormone Therapy and Dementia
Posted by on December 17, 2010 - 6:04pm

Hormone Therapy Use May Increase Or Decrease Dementia Risk Depending Upon Timing

Compared to women never on hormone therapy, those taking hormone therapy only at midlife had a 26 percent decreased risk of dementia; while women taking HT only in late life had a 48 percent increased risk of dementia, according to Kaiser Permanente researchers.   Women taking HT at both midlife (mean age 48.7 years) and late life had a similar risk of dementia as women not on HT, according to the study which appears in the Annals of Neurology. The study was funded in part by the National Institutes of Health.

Although previous research has shown that initiation of postmenopausal estrogen hormone therapy in late life increases the risk of dementia, animal studies and some observational studies have suggested that midlife use of HT may be beneficial. This is the first observational, long-term study to directly compare the effect of hormone therapy status in both midlife and late life on risk of dementia.

"This study is unique because we had a group of women who were on HT in midlife only and could look at their dementia risk over time, and we found a modest, protective association. We also found that if you start HT late in life, you have a 50 percent increased risk of dementia, which is consistent with other studies," said study lead author Rachel Whitmer, PhD, a research scientist with the Kaiser Permanente Division of Research in Oakland, Calif. "Women should speak with their doctor about what's best for their individual situation, however it appears from this study that women who are on short-term HT in midlife may benefit from a modest protective association, while initiation in late-life can cause harm."

Adjustment for high cholesterol, hypertension and stroke did not reduce the magnitude of the effect of late life HT on increased risk of dementia, according to the researchers. It's also possible that in the group of women who used HT both in midlife and late life; the potential modest benefit of midlife use was counteracted by a negative effect of late life use, they explained.

This study is part of an ongoing body of research at Kaiser Permanente to better understand the modifiable risk factors for dementia.

Limitations of this most recent study include the fact that HT information in midlife was self-reported and therefore researchers do not know the dose or type of HT involved. Also, because the pharmacy database was initiated in 1994, researchers do not have information on the duration of midlife HT.

Source: Kaiser Permanente

Does Estrogen Make You Smarter?
Posted by on November 26, 2010 - 10:17am

Scientists discover how estrogen works and flip its switch to reap benefits without risks

CHICAGO --- Estrogen is an elixir for the brain, sharpening mental performance in humans and animals and showing promise as a treatment for disorders of the brain such as Alzheimer’s disease and schizophrenia. But long-term estrogen therapy, once prescribed routinely for menopausal women, now is quite controversial because of research showing it increases the risk of cancer, heart disease and stroke.Northwestern Medicine researchers have discovered how to reap the benefits of estrogen without the risk. Using a special compound, they flipped a switch that mimics the effect of estrogen on cortical brain cells. The scientists also found how estrogen physically works in brain cells to boost mental performance, which had not been known.

When scientists flipped the switch, technically known as activating an estrogen receptor, they witnessed a dramatic increase in the number of connections between brains cells, or neurons. Those connections, called dendritic spines, are tiny bridges that enable the brain cells to talk to each other.

“We created more sites that could allow for more communication between the cells,” said lead investigator Deepak Srivastava, research assistant professor in neuroscience at Northwestern University Feinberg School of Medicine. “We are building more bridges so more information can go from one cell to another.”

Previous research has shown an increase in dendritic spines improves mental performance in animals. In humans, people who have Alzheimer’s disease or schizophrenia often have a decrease in these spines.

“We think there is a strong link between the number of dendritic spines and your mental performance,” Srivastava said. “A major theory is if you increase the number of spines, it could be a way to treat these significant mental illnesses. “

Northwestern scientists also found strong clues that estrogen can be produced in cortical brain cells. They identified aromatase, a critical protein needed to produce estrogen, to be in precisely the right spot in the brain cell to make more dendritic spines.

“We’ve found that the machinery needed to make estrogen in these brain cells is near the dendritic spines,” Srivastava said. “It’s exactly where it’s needed. There’s a lot of it in the right place at the right time. “

Next, Srivastava said, he wants to further identify the key molecules involved in the dendritic spine production and target them in the same way as the estrogen receptor in order to ultimately be able to treat schizophrenia and other mental disorders.

Nick Brandon, head of psychiatry at Pfizer Inc., whose group collaborated with the Penzes lab for this work, added, “We are very excited by the emerging data in this area. There is a great deal of literature and precedent for a role of estrogen and estrogen signaling in major mental illnesses. This adds to our understanding of the specific neuronal functions. As we understand the effects of these specific estrogen receptor beta compounds in preclinical models, we are discovering effects on specific neuronal functions, which could be relevant for the treatment of cognitive disorders, depression and schizophrenia. “

Marla Paul is the health sciences editor. Contact her at marla-paul@northwestern.edu

Alzheimer's Impacts Women Harder than Men
Posted by on November 12, 2010 - 10:59am

Alzheimer's disease affects twice as many women as it does men, according to a new report that portrays women as being "under siege" by the dreaded condition.

Created in conjunction with California first lady Maria Shriver, "The Shriver Report: A Woman's Nation Takes on Alzheimer's" shows that two-thirds of the people living with Alzheimer's are women, and 60 percent of Alzheimer's caregivers are women.  Shriver became involved in the issue when her father, Sargent Shriver, 94, was diagnosed with the disease in 2003.

The report finds that primary caregivers to Alzheimer's patients are six times more likely to develop the disease, or other forms of dementia, themselves, in part because of the emotional stress and physical demands of providing care to relatives and loved ones.

The estimated societal impact of the disease on government and businesses is $300 billion a year, according to the report.

Scripps Howard News Service

Study Suggests Gender/Sex Differences in Cognition Impairment
Posted by on September 24, 2010 - 2:47pm

Older men may be at risk of developing mild cognitive impairment (MCI), often a precursor to Alzheimer’s disease, earlier in life than older women, according to a study appearing today in Neurology. The study raises the question of whether there may be a gender difference in the development and progression of MCI.

Scientists evaluated the cognitive health of 1,969 dementia-free older people and found 16 percent showed signs of MCI, a condition usually marked by memory problems or other cognitive problems greater than those expected for their age. Prevalence was greater among the older participants, and it was consistently higher in men than women across all age ranges.

Ronald C. Petersen, Ph.D., M.D., and his team at the Mayo Clinic, Rochester, Minn., conducted the research.

"Because evidence indicates that Alzheimer's disease may cause changes in the brain one or two decades before the first symptoms appear, there is intense interest in investigating MCI and the earliest stages of cognitive decline," said National Institute on Aging (NIA)  Director Richard J. Hodes, M.D. "While more research is needed, these findings indicate that we may want to investigate differences in the way men and women develop MCI, similar to the way stroke and cardiovascular disease risk factors and outcomes vary between the sexes."

The researchers conducted in-person evaluations of 1,969 randomly selected people from all 70- to 89-year-olds living in Olmsted County, Minn. Results of the study indicated that:

  • Overall, MCI was more prevalent in men (19 percent) than in women (14 percent), even after adjusting for several demographic variables and clinical factors, such as hypertension and coronary artery disease.
  • Of the 16 percent affected with MCI, over twice as many people had the amnestic form that usually progresses to Alzheimer’s disease and the prevalence rate was higher in men than in women.
  • MCI prevalence was higher among people with the APOE e4 gene, a known risk factor for late-onset Alzheimer's, a form of the disease that usually occurs at age 65 or older.
  • A greater number of years spent in school was significantly associated with decreased MCI prevalence, from 30 percent among participants with less than nine years of education to just 11 percent in those with more than 16 years of education.
  • MCI prevalence was higher in participants who never married, as opposed to those currently or previously married.

The researchers noted that estimates of MCI prevalence vary in studies conducted around the world but generally fall into a range of 11 to 20 percent. The Mayo team's evaluation of participants included detailed in-person assessments that helped to capture the subtle changes in daily function that may mark the onset of MCI, Petersen said. The researchers also noted that the study’s limitations include a relatively low participation rate by Olmstead County residents and the fact that the population is predominantly white. Thus, these findings may not apply to other ethnic groups.

Source:  NIH National Institute on Aging