Showing posts with label cognitive functions. Show all posts
Showing posts with label cognitive functions. Show all posts

Monday, June 20, 2011

Low linguistic ability in early life linked to Alzheimer’s later on

Nun Study as unique source for the long-term Alzheimer’s research

In 1991, David A. Snowdon, Ph.D., Professor at Sanders-Brown Center on Aging College of Medicine, University of Kentucky, Lexington, began what has come to be known as the Nun Study. Participants in this study are 678 American members of the School Sisters of Notre Dame religious congregation. The nuns in the study are age 75 to 106.

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The Nun Study is an ongoing, one-of-a-kind resource for the study of brain diseases in the elderly. It is expected that data, tissue, and genetic material collected in this study will be used by scientists for decades into the future.

Each of the 678 participants in the Nun Study agreed to participate in annual assessments of their cognitive and physical function, medical exams, blood drawing for genetic and nutritional studies, and brain donation at death for neuropathologic studies. The Nun Study represents the largest brain donor population in the world. In addition, the sisters have given investigators full access to their convent and medical records. The convent archives are particularly useful in our study of Alzheimer's disease because they contain accurate risk factor data spanning the entire lifespan of the participants. Accurate information on early and mid-life risk factors is difficult or impossible to obtain in most other studies on Alzheimer's disease because individuals with this memory disorder cannot accurately recall their history. The convent archives contain a wealth of information including baptismal records, birth certificates, socioeconomic characteristics of the family, education documentation, autobiographies written in early, mid, and late life, as well as residential, social, and occupational data describing their mid and late lives.

Many factors that confound (or confuse) the findings of other studies are either eliminated or minimized because of the relatively homogeneous adult lifestyles and environments of these women. Participants in this study are non-smokers, drink little if any alcohol, have the same marital status and reproductive history, have lived in similar housing, held similar jobs, and had similar access to preventive and medical care.

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Findings from Nun Study

Some of the findings received from the Nun Study confirm the results, received from other researches, but there are some absolutely new insights obtained for the additional risk factors and causal relationship between personal characteristics and traits to the chance of the Alzheimer’s development at some moment in life.

Among the findings were:
1. Those, who had revealed better linguistic abilities in early life, were less likely to have dementia later.
2. Those, who demonstrated set of positive emotions in early life, had greater longevity.
3. Low linguistic ability in early life was associated both with dementia in later life and less longevity.
4. Those with low serum folate levels were more likely to have Alzheimer's disease of other dementia.
5. There was no significant relationship found between dental amalgams (silver fillings) and dementia.
6. Those with brain infarcts had poorer cognitive function and a higher prevalence of dementia.
7. Dementia was unrecognized by nursing staff in a number of cases.
8. Higher education in early life was associated with less cognitive decline in later life.

The study has confirmed, for example, that a history of stroke and head trauma can boost your chances of coming down with debilitating symptoms of Alzheimer's later in life; and that a college education and an active intellectual life, on the other hand, may actually protect you from the effects of the disease.

One of the most surprising results of the Nun Study, however, is the discovery that the way we express ourselves in language, even at an early age, can foretell how long we'll live and how vulnerable we'll be to Alzheimer's decades down the line. After analyzing short autobiographies of almost 200 nuns, written when they first took holy orders, he found that the sisters who had expressed the most positive emotions in their writing and who expressed the better linguistic abilities as girls ended up living longest, and that those on the road to Alzheimer's expressed fewer and fewer positive emotions as their mental functions declined.

So, the study found that low idea density shown in the writings of the young women was strongly linked with low cognitive test scores and the presence of Alzheimer's disease in late life. For example, the nuns with low idea density scores were 30 times more likely to do poorly on a standard measure of cognitive function, the Mini-Mental State Exam, than those with more complex writings. An even more dramatic difference was observed when cognitive ability and characteristics of brain tissue were compared in the nuns who died. Neurofibrillary tangles of Alzheimer's disease appeared in about 90 percent of those nuns who had low linguistic ability in early life.

Among other findings there are some, which still do not have the valid scientific explanation, as why there is not always the direct correlation between the medical evidence for the Alzheimer’s disease appearance in the brain and the actual behavioral symptoms doctors can see on these patients.

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"Most of the brains neatly fit our expectations, with little or no evidence of disease in a tack-sharp sister and abundant damage seen in a sister who had dementia," Dr. Snowdon wrote. "But sometimes (Dr. Bill) Markesbery (the neurologist who did the autopsies) finds little evidence of Alzheimer's in a sister who had the classic symptoms of the disease. And sometimes brains from other sisters who appeared mentally intact when alive show extensive evidence of the disease."

This surprising information wasn't a set-up by the researchers.  In fact, Dr. Snowdon noted that Dr. Markesbery was not informed prior to conducting the autopsy about the mental status of that particular sister. After the autopsy, Dr. Markesbery met with Dr. Snowdon and the study's neuropsychologist, Dr. Kathryn Riley, to compare notes.


In one case - that of Sister Maria - Dr. Markesbery found that the nun had some plaques and tangles, but the number was not large. The nun's brain itself weighed within the normal range (most Alzheimer's brains have lower weights). Furthermore, the sister's brain rated Stage II on the Braak scale. (The Braak scale defines six distinct stages of the disease based on an autopsy. Stage 0 indicates the general absence of tangles. Stages 1-VI described the increasing range of the number and spread of the tangles throughout the brain.)


Following Dr. Markesbery's report, Dr. Riley shared Sister Maria's scores on three evaluations conducted prior to her death. These evaluations showed that Sister Maria had suffered progressive loss of her mental, physical and social functions in a way that was consistent with Alzheimer's disease.


Yet the reverse can happen as well. For instance, Dr. Markesbery's autopsy of Sister Bernadette's brain yielded the findings that she had Braak Stage VI, which indicates the most severe presence of Alzheimer's. However, Dr. Riley's report on the cognitive evaluations conducted in the years prior to Sister Bernadette's death showed that the nun was mentally sharp.


 "The Nun Study's real eye-opening findings...are the ones that add to the evidence that Alzheimer's is not a yes/no disease," Dr. Snowdon wrote. "Rather it is a process - one that evolves over decades and interacts with many other factors." Using the data from the Nun's Study, Dr. Snowdon pointed out, "Of sisters in stages I or II, only 22 percent had evidence of dementia. For stages III and IV, that jumped to 43 percent. And by stages V and VI, 70 percent of the sisters had dementia."

While there is no magical cure for Alzheimer’s so far, the findings from Nun Study may give a hope that even you may not be able to eliminate the negative neurochemical changes in your brain, you still can fight the symptoms actual appearance by filling your life with regular physical and mental exercises, healthy diet, lowering stress, attempting to happy and present, etc. This way, you can be proactive in altering how this disease may affect you at some point, if you have predisposition, and follow in Sister Bernadette's footsteps, living a long and vital life.

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Monday, July 26, 2010

PET scans to predict Alzheimer's

Introduction

A PET scan (positron emission tomography) is imaging tests that can help reveal how your tissues and organs are functioning. To show this chemical activity, a small amount of radioactive material must enter your body.

The precise type of radioactive material, and its delivery method, depends on which organ or tissue is being studied by the PET scan. The radioactive material may be injected into a vein, inhaled or swallowed.

More radioactive material accumulates in areas that have higher levels of chemical activity. This often corresponds to areas of disease and shows up as brighter spots on the PET scan. A PET scan is useful in evaluating a variety of conditions — including neurological problems, heart disease and cancer.

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Recent researches confirmed that a PET scan can show the brain's biological changes attributable to Alzheimer's disease before any other diagnostic test with significant degree of the results reliability. Alzheimer's disease can even be detected several years earlier than the onset of symptoms. Early detection and confirmation of Alzheimer's disease allows for:
  • Early drug therapy to slow the loss of the patient's ability to function.
  • Future planning before loss of mental capacity.
  • Positive and accurate diagnosis of other dementing processes, chronic depression and normal aging.
  • Help in the discovery and development of new therapies.
  • Hope.
PET scan for Alzheimer’s

PET imaging has been confirmed as being one of the most accurate predictors of Alzheimer’s disease out of all of the different types of medical diagnostic imaging procedures available. A PET scan image of Alzheimers is able to show a physician the biological changes in the brain caused by Alzheimer’s disease. A recent study taken at UCLA, the California based university, have shown that PET imaging improves a doctor’s ability to forecast a patient’s future cognitive functions by up to 30%. This find relates to Alzheimer’s detection as PET imaging increases the ability of a physician to predict, in patients with early memory complaints, whether this condition will significantly worsen in the years following the initial exam.

PET scans for Alzheimer’s disease involves the administration of a radioactive tracer that is a combination of a radioisotope (a radioactive compound whose movements are detectable by a PET scanner) with a natural body compound. In Alzheimer’s diagnosis, the radioactive tracer used in the Positron Emission Tomography procedure is Fluorodeoxyglucose (FDG), which combines the natural body compound glucose with the radioisotope Fluorine-18. This radioactive tracer, or radiopharmaceutical, is used in Alzheimer’s diagnosis as the radioactive compound that it uses has a short half-life and will disappear from the body within hours. Therefore, PET scans for Alzheimer’s are safe and the patient should not have any worry about the radiation content of this procedure.

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Additionally, Alzheimer’s PET scans use FDG as it contains the body compound glucose. The use of FDG, which shares a similar structure to glucose, is important, as the absorption of glucose is effective in determining the metabolic activity of the brain. In Alzheimer’s disease and other forms of dementia, the brain produces a metabolic pattern that is significantly different from the metabolic pattern of healthy brain cells. As PET imaging examines the metabolic activity of brain cells by tracing how FDG is absorbed, it is able to detect Alzheimer’s disease and other forms of dementia.

Additionally, recent studies have confirmed the effectiveness of Positron Emission Tomography in distinguishing Alzheimer’s disease from other forms of dementia. This is because Alzheimer’s disease has a metabolic abnormality (bilateral temporoparietal hypometabolism) that is significantly different from metabolic abnormalities found in other forms of dementia.

PET scan of Alzheimer’s have increased in recent years as PET imaging provides a noninvasive, painless way for physicians to confirm the presence of Alzheimer’s in patients. Traditionally, autopsy or biopsy was considered the only methods to absolutely confirm the presence of Alzheimer’s disease. With PET technology, it is now possible to identify Alzheimer’s in its early phase and subsequently use new drug therapies to delay its progression.

Recent medical studies have pointed to the possible effectiveness of using PET scanning of the hippocampus as a way to detect Alzheimer’s disease while in its early stages. It is a well-known medical fact that the hippocampus, a region of the bran that is instrumental in learning and short-term memory, is affected in the early stages of Alzheimer’s disease. It is believed that through a PET scan of hippocampus that it will be possible to see the first signs of Alzheimer’s disease long before it has spread to the cerebral cortex, which damages cognitive function and impairs the memory. Future studies on the viability of a PET scan of hippocampus have been undertaken to further the use of PET scanning for detecting Alzheimer’s disease.

In the latest studies, a new type of PET scan has been used to detect Alzheimer's non-invasively. It also gives results that are as good as doing an autopsy. The brain of a person with Alzheimer's contains abnormal proteins that form deposits and tangles (or more specifically, amyloid senile plaques and tau neurofibrillary tangles) in the cortical region. However, the most reliable method of finding these proteins while the patient is alive is by surgical removal of brain tissue, an invasive and potentially risky procedure. Some scanning methods exist but they are not as reliable. Scientists have now come up with what appears to be a reliable non-invasive method of detecting these Alzheimer "markers" using a PET scan and a new tracer chemical called FDDNP that binds effectively to abnormal protein plaques and tangles.  A PET scan gives a three dimensional, computer enhanced and highly colorful "blurry-looking" image of the brain as it traces a positron emitting chemical (in this case FDDNP) after it is injected into the patient and travels through the tiny blood vessels in the brain. Any abnormal protein plaques and tangles show up because the FDDNP will stick to them.

While the usefulness of the PET scan results for early Alzheimer’s detection is already proven, the potential for this method is still huge, so we will see more and more intense research in this direction and hopefully even more promising results.

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Tuesday, April 6, 2010

Predicting Alzheimer ’s Disease Progression Rate

Mental status exam - Mental status exams assess memory, concentration, and other cognitive skills. The most frequently used mental status exam is called the Mini-Mental State Exam (MMSE), a research-based set of questions that results in a score representing a person's general level of cognitive functioning.

The MMSE is generally a reliable and valid indicator of cognitive impairment that can correctly distinguish between individuals with dementia, individuals with pseudo-dementia due to depression, and individuals with depression and no cognitive impairment. However, the test must be used with caution in certain groups of people. For example, highly educated people frequently score high on the MMSE, even if they have Alzheimer's Disease (AD). Similarly, people with less than an eighth grade education or whose first language is not English often score poorly on the MMSE, even though they may not have cognitive impairment.

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The latest research states that not only the patient current mental status may be evaluated based on the MMSE assessment results, but also Alzheimer's disease (AD) progression rate. The new approach is able to reliably predict how quickly the individual patient will lose cognitive and other abilities with significant degree of reliability.

Rachelle Doody, MD, PhD, and colleagues from Baylor College of Medicine in Houston, Texas, report initial results using the prognosis indicator with 597 patients followed up for 15 years published online February 23, 2010 in Alzheimer's Research & Therapy.

“Patients and families frequently ask clinicians to predict expected rates of cognitive and functional decline, and clinicians currently have little basis for making such decisions," Dr. Doody told Medscape Neurology.

"We’ve found that a simple, calculated progression rate at the initial visit gives reliable information regarding performance over time," she said. "The slowest progression group also survives longer."

Calculating AD Progression Rate

The pre-progression rate is calculated using a standard assessment of symptom duration in years and the baseline Mini-Mental State Examination (MMSE) score. The estimate of duration includes a series of questions about the duration of specific symptoms that might be a sign of AD, medical records review, and informant interview.

The study authors explain, “Since a cognitively intact individual should obtain the maximum MMSE score of 30, the pre-progression rate is given by the formula: (30 baseline MMSE)/estimated duration of symptoms in years.”

Those with an MMSE score decrease of less than 2 points per year were classified as slow progressors. Intermediate progressors were defined as having a 2- to 4-point decrease per year and rapid progression as a 5 point or greater decrease per year in MMSE score.

Dr. Doody told Medscape Neurology, “The procedures for obtaining and using the information are not yet in common use, but they could be. With further refinement, physicians could use this work to tell patients whether they fall into a slow, intermediate, or rapidly progressing category with respect to the intrinsic progression of their AD. They might decide upon follow-up intervals and how aggressive to be with medications based upon the progression rate. Once started on therapy, it might be possible to alter the intrinsic rate, but this requires further study.”

The researchers examined outcomes for patients annually for up to 15 years using the MMSE, the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAScog – cognitive MMSE sub-scale), the Verbal Series Attention Test, the Clinical Dementia Rating Scale Sum of Boxes, and the Lawton and Brody Activities of Daily Living Scale, which combines the Physical Self-Maintenance Scale and the Instrumental Activities of Daily Living Scale.

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Slow Progressors Also Live Longer

The investigators found that patients in the slow and intermediate groups maintained better performance on tests of cognitive function, global function, and complex activities of daily living than the rapid progressors. For example, slow progressors gained 0.6 fewer points per year on the ADAScog and intermediate progressors 0.8 fewer points per year than rapid progressors.

At study entry, the slow progressors also had a longer estimated duration of symptoms than intermediate or fast progressors, as well as higher IQ and education.

Slow progressors also lived longer. Median survival was 4.7 years for slow, 4.1 years for intermediate, and 2.5 years for rapid progressors, adjusted for age, sex, education, and baseline severity (hazard ratio, 0.62 for slow vs. fast progressors).

“Our results suggest that prognostications based upon initial progression rate are most reliable for slow and fast progressors but that long duration reliability of an intermediate progression rate may depend upon the patient's age and life expectancy at diagnosis," the study authors conclude. "It would be safe to say that an intermediate progressor may remain so for several years, but that, if the patient lives for a long time after diagnosis, the rate may increase sufficiently to affect both abilities and survival."

Next Question: Can Drugs Alter Progression Rate?

Whether these “apparently intrinsic” progression rates can be modified by anti-dementia drug treatment is a key unanswered question that must be answered before the progression rate tool can be adopted for clinical use, the study authors say.

For now, Dr. Doody said, “Physicians could tell patients that people do not progress naturally at the same rate and that their individualized progression characteristics should be taken into account in planning their treatment and in monitoring their response to therapy. They could also say that the proposed rate requires some procedures that are not yet in everyday use (a standardized estimate of duration) and that they will decide over time whether or not to incorporate these procedures into what they do based upon continued studies of its utility.”

This study also has implications for AD clinical trial design. “Currently, parallel group studies count on randomization to yield comparable placebo and treatment groups," the study authors write. "Preprogression rates are not assessed, yet imbalances across the treatment groups in this important variable could obscure or create treatment differences. Future clinical trials may benefit from gathering systematic data regarding individual symptom onset in order to perform a formal estimate of duration and to calculate preprogression rates.”
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Not Ready for Routine Use

Cognitive neurologist Alireza Atri, MD, PhD, agreed that this might be useful. Dr. Atri, who recently analyzed long-term effectiveness of combination therapy in AD (Alzheimer Dis Assoc Disord. 2008;11:209-221), is director of the Memory Disorders & Special Dementia Units at the Veterans' Affairs Geriatric Research Education and Clinical Center in Bedford, Massachusetts, and assistant in neurology at Massachusetts General Hospital/Harvard Medical School in Boston.

Asked by Medscape Neurology to comment on this study, Dr. Atri said, “I think this is an important study with several exceptional strengths, including utilization of a large, well-characterized longitudinal clinical cohort with useful measure and endpoints and analysis using sophisticated methods guided by good clinical and scientific knowledge from a leader in the field who has an uncommon perspective and expertise, working at the interface of clinical care and clinical trials and utilizing quantitative methodology to address important questions with great practical implications that, thus far, have been mostly neglected, overlooked, and/or underappreciated.”

Dr. Atri noted that although this model for predicting risk and prognosis in AD is not yet ready for routine use, it “provides a very good enhancement/upgrade from previous work and prognostication models, including some of Dr. Doody's own work, that integrate patient demographics and clinical characteristics and measures, including test scores, type and duration of symptoms, and physical exam findings, at a first clinical visit to a neurologist/physician in order to better predict the highly variable individual course we see in patients with Alzheimer's disease.”

Dr. Atri said that the study raises questions that need to be addressed further, including the effect of antidementia medications, vitamins and dietary supplements, vascular risk factors, behavioral symptoms, physical findings, especially parkinsonism and extrapyramidal signs, and genetic susceptibility factors, such as APOE-e4 status.

“We are a ways away still, but we desperately need to be wiser and more efficient in our approaches to gathering and using clinical data," Dr. Atri said. "I agree that clinical trials should heed Dr. Doody’s findings and incorporate more data and approaches like this to minimize risk of imbalances between or within treatment groups that can easily obscure signals of efficacy in Alzheimer's disease trials.”

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