Alzheimer’s Diagnostic Guidelines Updated for First Time in 27 Years

For the first time in 27 years, clinical diagnostic criteria for Alzheimer’s disease dementia have been revised, and research guidelines for earlier stages of the disease have been characterized to reflect a deeper understanding of the disorder.

The National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease outline some new approaches for clinicians and provides scientists with more advanced guidelines for moving forward with research on diagnosis and treatments. They mark a major change in how experts think about and study Alzheimer’s disease. Development of the new guidelines was led by the National Institutes of Health and the Alzheimer’s Association.

The original criteria were the first to address the disease and described only later stages, when symptoms of dementia are already evident. The updated guidelines announced today cover the full spectrum of the disease as it gradually changes over many years. They describe the earliest preclinical stages of the disease, mild cognitive impairment, and dementia due to Alzheimer’s pathology. Importantly, the guidelines now address the use of imaging and biomarkers in blood and spinal fluid that may help determine whether changes in the brain and those in body fluids are due to Alzheimer’s disease. Biomarkers are increasingly employed in the research setting to detect onset of the disease and to track progression, but cannot yet be used routinely in clinical diagnosis without further testing and validation.

“Alzheimer’s research has greatly evolved over the past quarter of a century. Bringing the diagnostic guidelines up to speed with those advances is both a necessary and rewarding effort that will benefit patients and accelerate the pace of research,” said National Institute on Aging Director Richard J. Hodes, M.D.

“We believe that the publication of these articles is a major milestone for the field,” said William Thies, Ph.D., chief medical and scientific officer at the Alzheimer’s Association. “Our vision is that this process will result in improved diagnosis and treatment of Alzheimer’s, and will drive research that ultimately will enable us to detect and treat the disease earlier and more effectively. This would allow more people to live full, rich lives without — or with a minimum of — Alzheimer’s symptoms.”

The new guidelines appear online April 19, 2011 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. They were developed by expert panels convened last year by the National Institute on Aging (NIA), part of the NIH, and the Alzheimer’s Association. Preliminary recommendations were announced at the Association’s International Conference on Alzheimer’s Disease in July 2010, followed by a comment period.

Guy M. McKhann, M.D., Johns Hopkins University School of Medicine, Baltimore, and David S. Knopman, M.D., Mayo Clinic, Rochester, Minn., co-chaired the panel that revised the 1984 clinical Alzheimer’s dementia criteria. Marilyn Albert, Ph.D., Johns Hopkins University School of Medicine, headed the panel refining the MCI criteria. Reisa A. Sperling, M.D, Brigham and Women’s Hospital, Harvard Medical School, Boston, led the panel tasked with defining the preclinical stage. The journal also includes a paper by Clifford Jack, M.D., Mayo Clinic, Rochester, Minn., as senior author, on the need for and concept behind the new guidelines.

The original 1984 clinical criteria for Alzheimer’s disease, reflecting the limited knowledge of the day, defined Alzheimer’s as having a single stage, dementia, and based diagnosis solely on clinical symptoms. It assumed that people free of dementia symptoms were disease-free. Diagnosis was confirmed only at autopsy, when the hallmarks of the disease, abnormal amounts of amyloid proteins forming plaques and tau proteins forming tangles, were found in the brain.

Since then, research has determined that Alzheimer’s may cause changes in the brain a decade or more before symptoms appear and that symptoms do not always directly relate to abnormal changes in the brain caused by Alzheimer’s. For example, some older people are found to have abnormal levels of amyloid plaques in the brain at autopsy yet never showed signs of dementia during life. It also appears that amyloid deposits begin early in the disease process but that tangle formation and loss of neurons occur later and may accelerate just before clinical symptoms appear.

To reflect what has been learned, the National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease cover three distinct stages of Alzheimer’s disease:

  • Preclinical — The preclinical stage, for which the guidelines only apply in a research setting, describes a phase in which brain changes, including amyloid buildup and other early nerve cell changes, may already be in process. At this point, significant clinical symptoms are not yet evident. In some people, amyloid buildup can be detected with positron emission tomography (PET) scans and cerebrospinal fluid (CSF) analysis, but it is unknown what the risk for progression to Alzheimer’s dementia is for these individuals. However, use of these imaging and biomarker tests at this stage are recommended only for research. These biomarkers are still being developed and standardized and are not ready for use by clinicians in general practice.
  • Mild Cognitive Impairment (MCI) — The guidelines for the MCI stage are also largely for research, although they clarify existing guidelines for MCI for use in a clinical setting. The MCI stage is marked by symptoms of memory problems, enough to be noticed and measured, but not compromising a person’s independence. People with MCI may or may not progress to Alzheimer’s dementia. Researchers will particularly focus on standardizing biomarkers for amyloid and for other possible signs of injury to the brain. Currently, biomarkers include elevated levels of tau or decreased levels of beta-amyloid in the CSF, reduced glucose uptake in the brain as determined by PET, and atrophy of certain areas of the brain as seen with structural magnetic resonance imaging (MRI). These tests will be used primarily by researchers, but may be applied in specialized clinical settings to supplement standard clinical tests to help determine possible causes of MCI symptoms.
  • Alzheimer’s Dementia — These criteria apply to the final stage of the disease, and are most relevant for doctors and patients. They outline ways clinicians should approach evaluating causes and progression of cognitive decline. The guidelines also expand the concept of Alzheimer’s dementia beyond memory loss as its most central characteristic. A decline in other aspects of cognition, such as word-finding, vision/spatial issues, and impaired reasoning or judgment may be the first symptom to be noticed. At this stage, biomarker test results may be used in some cases to increase or decrease the level of certainty about a diagnosis of Alzheimer’s dementia and to distinguish Alzheimer’s dementia from other dementias, even as the validity of such tests is still under study for application and value in everyday clinical practice.

The panels purposefully left the guidelines flexible to allow for changes that could come from emerging technologies and advances in understanding of biomarkers and the disease process itself.

“The guidelines discuss biomarkers currently known, and mention others that may have future applications,” said Creighton H. Phelps, Ph.D., of the NIA Alzheimer’s Disease Centers Program. “With researchers worldwide striving to develop, validate and standardize the application of biomarkers at every stage of Alzheimer’s disease, we devised a framework flexible enough to incorporate new findings.”

Source: NIH

Cognitive and Physical Decline in Older Adults Associated with Severe Sepsis

Older adults who survive hospitalization involving severe sepsis, a serious medical condition caused by an overwhelming immune response to severe infection, are at higher risk for cognitive impairment and physical limitations than older adults hospitalized for other reasons, researchers have found.

The research, conducted by the University of Michigan and supported primarily by the National Institute on Aging (NIA), part of the NIH, appears in the Oct. 27, 2010, issue of the Journal of the American Medical Association.

Theodore J. Iwashyna, M.D., Ph.D., and colleagues found that an older person’s risk of cognitive decline increased almost threefold following hospitalization for severe sepsis. They also found that severe sepsis was associated with greater risk for the development of at least one new limitation in performing daily activities following hospitalization.

“Sepsis is common in older people and has a high mortality rate,” said NIA Director Richard J. Hodes, M.D. “This study shows that surviving sepsis may bring substantial and under-recognized problems with major implications for patients, families and the health care system.”

In sepsis, immune system chemicals released into the blood to combat serious infection trigger widespread inflammation. This can lead to low blood pressure, heart weakness, and organ failure. Anyone can get sepsis, but infants, children, older people, and those with weakened immune systems are most vulnerable. People with sepsis often receive treatment in hospital intensive care units to combat the infection, support vital organs and prevent a drop in blood pressure.

“This study should help change the way we think about severe sepsis,” said Iwashyna. “We usually think of severe sepsis as a medical emergency and focus our efforts on making sure the patient survives. This study shows that survivors often have severe problems for years afterwards.”

Using data from the NIA-supported Health and Retirement Study (HRS), the researchers analyzed the cognitive and physical function of older people before and after hospitalization for severe sepsis. The HRS is a long-term study that collects information on the health, economic and social factors influencing the health and well-being of a nationally representative sample of Americans over age 50. Study data on participants 65 and older are linked to Medicare claims data to enable detailed analysis of medical conditions and health status.

The scientists analyzed Medicare claims data from 516 people who survived 623 hospitalizations for severe sepsis between 1998 and 2005. The average age of participants was 77 at the time of hospitalization. The researchers also examined the individuals’ HRS data on cognitive function, measured through standard tests. Physical limitations were measured by the need for assistance in six activities of daily living basic self-care tasks (walking, dressing, bathing, eating, toileting and getting into and out of bed) and five instrumental activities of daily living (preparing a hot meal, shopping for groceries, making telephone calls, taking medicines and managing money), which are associated with the ability to live independently. For comparison, the researchers analyzed Medicare and HRS data on 4,517 survivors of 5,574 non-sepsis general hospitalizations during this time period.

Almost 60 percent of hospitalizations for severe sepsis were associated with worsened cognitive and/or physical function among survivors in the first survey following hospitalization. The risk of progression to moderate or severe cognitive impairment in sepsis survivors was 3.33 times higher than their risk before hospitalization. Severe sepsis was associated with the development of 1.57 new functional limitations among patients with no limitations before sepsis. In contrast, patients who did not develop sepsis and had no functional limitations before hospitalization developed an average of 0.48 new functional limitations. Non-sepsis hospital admissions were not associated with an increased risk for cognitive decline.

“This is one of more than a thousand research papers that have used Health and Retirement Study data,” said Richard Suzman, Ph.D., director of the NIA’s Division of Behavioral and Social Research, which supports the HRS. “The uniquely rich HRS dataset enabled the analysis of both cognitive and physical function in relation to hospitalization for a very specific medical condition. I look forward to the investigators refining their findings in the future.”

Source: NIH, October 26, 2010

Alzheimer’s Disease Risk Different for Men and Women

Recent research suggests that the chances of developing Alzheimer’s Disease are different for men and women, with stroke in men and depression in women being key elements.

The research was conducted in France, among 7,000 people aged 65 and over, drawn from the general population. While none of the participants had dementia, some 40% had mild cognitive impairment. Four years later 6.5% of those displaying mild cognitive impairment had developed dementia, while no change was noted in just over half. About one third returned to normal cognitive ability.

The move from cognitive impairment to dementia however, was marked among subjects taking anticholinergic drugs for depression. A variation in the ApoE gene, a known risk factor for dementia, was also more common among those whose mild cognitive impairment progressed.

The results demonstrated that men with mild cognitive impairment were probably overweight and diabetic, and to have suffered a stroke. In fact, male stroke victims were three times as likely to progress from cognitive impairment to dementia.

Women with mild cognitive impairment had poorer general health, were disabled, and suffered from insomnia, besides having an inadequate support group. They were also unable to perform the daily tasks that would enable them to live alone without assistance. It was judged they were 3.5 times as likely to develop dementia, while those suffering from depression were twice as likely to do so. Stroke was not a risk factor for women, although there was similar rate of occurrence in men and women.

Source: Journal of Neurology, Neurosurgery, and Psychology, 2008; doi 10.1136/jnnp.2007.136903

Alcohol May Cause Lower Brain Volume

According to a recent report, the more you drink the smaller your brain becomes. It is estimated that 1.9 percent decrease in brain volume per decade accompanies an increase in white matter lesions.

The progression of dementia and problems with thinking, learning and memory are accompanied by lower brain volumes and larger white matter lesions. Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease; because the brain receives blood from this system, researchers have hypothesized that small amounts of alcohol may also attenuate age-related declines in brain volume. The study results were published in the October, 2008 issue of Archives of Neurology.

Members of the Framingham Offspring Study, which began in 1971 and included 1,839 adults with an average age of 60, were studied by Carol Ann Paul, M.S., of Wellesley College, Mass., and colleagues. The Study also included children of the original Framingham Heart Study participants and their spouses. Between 1999 and 2001, participants underwent magnetic resonance imaging (MRI) and a health examination. They reported the number of alcoholic drinks they consumed per week, along with their age, sex, education, height, body mass index and Framingham Stroke Risk Profile (which calculates stroke risk based on age, sex, blood pressure and other factors).

“Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers,” the authors write. “There was a significant negative linear relationship between alcohol consumption and total cerebral brain volume.”

Although men were more likely to drink alcohol, the association between drinking and brain volume was stronger in women, they note. This could be due to biological factors, including women’s smaller size and greater susceptibility to alcohol’s effects.

“The public health effect of this study gives a clear message about the possible dangers of drinking alcohol,” the authors write. “Prospective longitudinal studies are needed to confirm these results as well as to determine whether there are any functional consequences associated with increasing alcohol consumption. This study suggests that, unlike the associations with cardiovascular disease, alcohol consumption does not have any protective effect on brain volume.”

Source: Archives of Neurology,

Cognitive Impairment Among Older Americans Decreasing

A recent study shows a downward trend in the rate of cognitive impairment among people aged 70 and older. The study was led by two University of Michigan Medical School physicians and their colleagues, and is based on data from the Health and Retirement Study (HRS), a national survey of older Americans funded by the National Institute on Aging and based at the U-M Institute for Social Research (ISR).

"From these results, we can say that brain health among older Americans seems to have improved in the decade studied, and that education and wealth may be a big piece of the puzzle," says lead author Kenneth Langa, M.D., Ph., an associate professor of internal medicine who also holds appointments in ISR and the VA Ann Arbor Healthcare System.

Between 1993 and 2002 the incidence of cognitive impairment in this age group decreased by 3.5%, or hundreds of thousands of people. The reasons for this decline are not yet known, but the authors of the survey state that older people today have had more formal education, higher economic status and better care for risk factors—high blood pressure, high cholesterol, and smoking – that can endanger their brains. Of the 11,000 people in the study, those with more formal education and personal wealth were less likely to have cognitive problems.

The study was publishe in the the online edition of the journal Alzheimer’s and Dementia.

Source: Alzheimer’s & Dementia, Feb 18, 2008, online edition.

Study Suggests Folate Deficiency Increases Dementia Risk Three-Fold

Recent research suggests that the risk of dementia in elderly people is increased three times by a lack of folate.

518 people were monitored for the development of dementia during the years 2001 through 2003. All subjects were aged 65 and over and lived in either a rural or urban community in the southern part of the country. Tests were carried out at the beginning and end of the 2-year period to check for any dementing illnesses. Blood tests were also conducted to measure levels of folate, vitamin B12, and the protein homocysteine, and how these changed over time. High levels of homocysteine have been associated with cardiovascular disease.

At the beginning of 2001, almost 20% of people monitored hd high levels of homocysteine, 3.5% were folate deficient, and 17% had low vitamin B12 levels.The higher the beginning levels of folate, the higher were vitamin B12 levels, and the lower were those of homocysteine.

By the end of 2003, 45 people had developed dementia, and of these 34 had Alzheimer’s disease, 7 had vascular dementia and 4 had other types of dementia. It was observed that dementia was more probable in the older, poorly educated and inactive subjects, and among those who had deposits of th protein ApoE.

People whose folate levels fell during the 2-year period were significantly more likely to develop dementia, while their homocysteine levels rose. People who were folate deficient to begin with, were almost 3.5 times more likely to develop dementia.

The research was published in the Journal of Neurology Neurosurgery and Psychiatry.

Source: J Neurol Neurosurg Psychiatry 2008; doi 10.1136/jnnp.2007.131482

Elevated Blood Pressure May Result in Mild Cognitive Impairment

A report in the December, 2007 issue of Archives of Neurology claims that high blood pressure can increase the risk of mild cognitive impairment, affecting the ability to thinking and learning.

About 9.9 of every 1000 elderly people who do not have dementia develop mild cognitive impairment early, and of these, 10%-12% develop Alzheimer’s disease. compared with 1%-2% of the general population. Dr. Christiane Reitz, M.D., Ph.D., and colleagues at the Columbia University Medical Center, New York, monitored 918 Medicare patients with an average age of 76.3 years, starting in 1992 through 1994. None had any mild cognitive impairment. Participants were then checked every 18 months, for an average of 4.7 years. People with mild cognitive impairment registered low cognitive scores and a defective memory, but were not diagnosed with dementia.

334 people developed mild cognitive impairment during the follow-up phase— including 160 cases of amnestic mild cognitive impairment, and 174 cases of non-amnestic mild cognitive impairment. High Blood pressure was connected with an increased risk of all types of mild cognitive impairment that was mostly associated with an increased risk of non-amnestic mild cognitive impairment. Hypertension was not associated with amnestic mild cognitive impairment, or a change in memory and language

"The mechanisms by which blood pressure affects the risk of cognitive impairment or dementia remain unclear," the authors write. "Hypertension may cause cognitive impairment through cerebrovascular disease. Hypertension is a risk factor for subcortical white matter lesions found commonly in Alzheimer’s disease. Hypertension may also contribute to a blood-brain barrier dysfunction, which has been suggested to be involved in the cause of Alzheimer’s disease. Other possible explanations for the association are shared risk factors," including the formation of cell-damaging compounds known as free radicals.

The authors believe that their findings support the hypothesis that hypertension increases the risk of incident mild cognitive impairment, especially non-amnestic mild cognitive impairment They conclude that preventing and treating hypertension may be important in lowering the risk of cognitive impairment.

Source: American Medical Association (AMA)

One in Seven Americans Over 70 Has Dementia

A new analysis suggests that about 3.4 million Americans over 70 years of age—one in seven people in that age group—has dementia, and 2.4 million of them have Alzheimer’s disease (AD).

The study was published online this week in Neuroepidemiology, and is the first to estimate rates of dementia and AD using a nationally representative sample of older adults across the United States.

The study highlights the nationwide reach of dementia, which affects not only those with the disease, but their families and communities as well. "As the population ages during the next few decades, the prevalence of Alzheimer’s disease will increase several-fold unless effective interventions are discovered and implemented," said National Institute on Aging Director Richard J. Hodes, M.D. "These data underscore the urgency of research in this area."

The study included 856 HRS participants over the age of 70 from 42 states in 2001-2003. Aging, Demographics and Memory Study (ADAMS) interviewers from Duke University Medical School conducted at-home evaluations to gather information about each participant’s cognitive and functional status and symptoms, neuropsychiatric symptoms, current medications, medical history and family history of memory problems. Prior neuroimaging and laboratory results were also obtained.

A team of clinicians reviewed the evaluation information and made a preliminary assessment of each person’s cognitive status. A consensus panel of other medical experts then used well-accepted diagnostic criteria to determine if the participant had normal cognitive function, cognitive impairment without dementia, or dementia. Such criteria further were used to discern the type of dementia, including AD or vascular dementia, the second most common cause of dementia in older adults.

Based on the experts’ classifications, Drs. Plassman and Langa and co-authors estimated the national prevalence and total numbers of people age 71 and older, by age group, with any dementia and with AD or vascular dementia in 2002. According to their calculations, 13.9 percent of Americans age 71 and older have some type of dementia, 9.7 percent of Americans in that age group have AD, and 2.4 percent have vascular dementia. AD accounted for about 70 percent of all dementia cases among people 71 and older.

As in other studies, the ADAMS analysis showed that the prevalence of dementia increases significantly with age. Five percent of people ages 71 to 79, 24.2 percent of people 80 to 89, and 37.4 percent of those 90 years or older were estimated to have some type of dementia. The estimated rate of Alzheimer’s also rose greatly with older age — from 2.3 percent of people ages 71 to 79 to 18.1 percent of people 80 to 89 to 29.7 percent of those age 90 and older. The ADAMS investigators found fewer years of education and the presence of at least one APOE e4 allele, a genetic risk factor for AD, to be strong predictors of AD and other dementias.

Richard Suzman, Ph.D., director of NIA’s Behavioral and Social Research Program, which jointly directs the HRS, said the ADAMS data will prove particularly valuable not only in assessing the prevalence of dementia, but also its impact. "ADAMS, with its link to the data about the health, economic, and family resources of individuals in the study, will help us to characterize more fully the burden of dementia on individuals, caregivers and the nation’s health care system," he says.

The ADAMS report is the latest published study to estimate the prevalence of dementia and AD among older Americans. "These assessments have provided a range of estimates, based on differing methodologies and approaches," explains Dallas Anderson, Ph.D., program director for population studies in NIA’s Dementias of Aging Branch.

For example, some studies have included lower age ranges than ADAMS or broader characterizations of dementia, or have sampled participants in a specific community as a base for national extrapolations. A study reported in 1998 (Brookmeyer et al., 1998) combined incidence data from four community-based studies, estimating that national Alzheimer’s prevalence among individuals age 60 years or older would rise from 2.3 million in 1997 to 8.6 million in 2047. Widely cited estimates based on the prevalence of Alzheimer’s disease in a Chicago-based community (Hebert et al., 2003), and an earlier comparable study using data from East Boston (Evans et al., 1990) forecast the number of those age 65 or older with AD to be 5.1 million in 2010.

Despite the varied approaches and findings, however, NIA experts point out, the numbers of people with dementia, and Alzheimer’s specifically, will certainly increase until ways to delay the progression or prevent the dementia are found. Advancing age is the most common known risk factor for Alzheimer’s disease.

The HRS is an ongoing national survey of 22,000 adults age 51 and older that began in 1992, providing data that helps researchers, policy makers and others understand the life circumstances of older adults and help address the challenges of the nation’s rapidly aging population.

NIA leads the federal effort supporting and conducting research on aging and the medical, social and behavioral issues of older people, including AD and age-related cognitive change.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.

Brenda L. Plassman, Ph.D., of Duke University Medical Center, with Kenneth M. Langa, M.D., Ph.D., and David R. Weir, Ph.D., of the University of Michigan, Robert B. Wallace, Ph.D., of the University of Iowa, and others, conducted the analysis as part of the Aging, Demographics and Memory Study (ADAMS). ADAMS is a sub-study of the larger Health and Retirement Study (HRS), the leading resource for data on the combined health and economic circumstances of Americans over age 50. ADAMS and the HRS are sponsored by the National Institute on Aging, a component of NIH, under a cooperative agreement with the University of Michigan.

Source: National Institutes of Health, October 30, 2007

Rate of Memory Loss Greater in Dementia Patients With More Education

According to a recent study in the journal Neurology, while higher education levels initially delay the onset of dementia, once dementia starts, the rate of memory loss is more rapid than in less educated individuals.

According to study author Charles B. Hall, PhD of the Albert Einstein College of Medicine, "our study showed that a person with 16 years of formal education would experience a rate of memory decline that is 50% faster than someone with just four years of education."

The study started in the 1980s, and monitored 488 people born between 1894 and 1906, with study findings based on the 117 members of the sample who eventually developed Alzheimer’s or some other form of dementia. Study participants ranged from people with postgraduate education to people with less than three years of elementary school education.

Dr. Hall believes that this rapid decline in the more educated people might be explained by their having a greater cognitive reserve, or the brain’s ability to maintain function in spite of damage. This meant that while patients are often diagnosed with dementia at a later date, once the cognitive reserve is no longer able to compensate for the damage that has occurred, then the symptoms emerge.

The study is valuable, says Dr. Hall, because it examines memory loss before a formal diagnosis of Alzheimer’s.

The study was supported by the National Institute on Aging. Other researchers from the Einstein Aging Study involved in the research included Carol Derby, PhD; Aaron LeValley, MA; Mindy J. Katz, MPH; Joe Verghese, MD; and Richard B. Lipton, MD.

Source: Neurology, October 23, 2007

Researchers Find Major Clues on How Schizophrenia Develops

Scientists have found some major clues in learning more about why schizophrenia develops. The new research may lead to better medications to correct gene-related problems that can lead to schizophrenia.

The researchers found that a gene called GAD1, which makes an enzyme essential for production of the chemical messenger called GABA, is turned on at increasingly high rates during normal development of the prefrontal cortex, but that this normal increase may not occur in people with schizophrenia. The prefrontal cortex is involved in higher functions like thinking and decision-making.

While scientists have known that abnormalities in brain development and in GABA synthesis play a role in schizophrenia, this study shows that defects in specific biochemical reactions that regulate gene activity—such as turning genes on and off so that they can make substances like the GAD1 enzyme—are also involved.

"This discovery opens a new area for exploration of schizophrenia," said NIMH Director Thomas R. Insel, MD. "Studies have yielded very strong evidence that schizophrenia involves a decrease in the enzymes, like GAD1, that help make the neurotransmitter GABA. Now we’re starting to identify the mechanisms involved, and our discoveries are pointing to potential new targets for medications."

The researchers also found that people with three different variations of the GAD1 gene that have been associated with schizophrenia also were more likely to have indicators of a malfunction in brain development. Among them were indicators of altered epigenetic actions related to GABA synthesis.

Clozapine and other antipsychotic medications are effective for many patients, but some patients choose to discontinue treatment because of the side effects they experience on these drugs. For this reason, scientists are working to find more precise molecular targets for the development of new medications that can correct the epigenetic flaws.

"We’ve known that schizophrenia is a developmental disease, and that something happens in the maturation of the prefrontal cortex during this vulnerable period of life. Now we’re beginning to find out what it is, and that sets the stage for better ways of preventing and treating it," says the study’s lead author, Schahram Akbarian, MD, PhD.

Results of the research were published in the October 17 issue of the Journal of Neuroscience, by Schahram Akbarian, MD, PhD, Hsien-Sung Huang, PhD student, and colleagues at the University of Massachusetts Medical School and Baylor College of Medicine. The study was funded by the National Institutes of Health’s National Institute of Mental Health (NIMH) and National Institute of Child Health and Human Development.

Sources:

  • National Institutes of Health
  • Journal of Neuroscience, October 17, 2007