Jan 252011
 

Using a new technology that relies on thousands of synthetic molecules to fish for disease-specific antibodies, researchers have developed a potential method for detecting Alzheimer’s disease with a simple blood test. The same methodology might lead to blood tests for many important diseases, according to the report published by Thomas Kodadek’s group at the Scripps Research Institute in the January 7th issue of the journal Cell.

The new method relies on the notion that many diseases lead to the production of modified proteins. At some point, the adaptive immune system might begin to recognize those proteins as foreign and mount a response. If tests could be developed to recognize those disease-specific proteins or the antibodies that recognize them, it could be the basis for early diagnosis. But in most cases, researchers have had little luck identifying those abnormal proteins.

Kodadek’s team decided to take a different tack. They used a large library of randomly selected, unnatural molecules known as “peptoids” to screen for antibodies found in the bloodstream of animals or patients with specific diseases and not in healthy controls.

Their method uncovered three peptoids that appear to discriminate between healthy and Alzheimer’s disease blood samples with high accuracy. Three of them reacted strongly to the blood of six patients with the condition, but not that of 16 healthy individuals used as controls. Although this is encouraging the findings must be corroborated by further studies to demonstrate that antibodies can indicate whether the attack opens a picture for diagnosing the disease.

* Reddy MM, Wilson R, Wilson J, Connell S, Gocke A, Hynan L, German D, Kodadek T. Identification of candidate IgG biomarkers for Alzheimer’s disease via combinatorial library screening. Cell 2011 January 7;144:132-142.

Michael S. Rafii, M.D., Ph.D.
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

Jan 162011
 

Dear Readers,

I was recently on a conference call with women physicians discussing the latest in Women’s Health and was asked about vitamin D and its effect on cognition. Indeed vitamin D has received a lot of media attention lately; attention focused on its potential effect on cardiovascular and bone health, in addition to its anti-inflammatory and anti-oxidative effects. Thus, it was not a surprise to me when the discussion turned to “cognitive health” and whether or not (1) vitamin D levels were associated with cognitive function and (2) whether its supplementation would provide an “added cognitive benefit” to female patients.

At the time the question was posed, I immediately thought about an article I read in Neurology that examined whether weekly dietary intake of vitamin D was associated with cognitive function in older women. Participants in this study came from the EPIDOS, a French community dwelling cohort study that was designed to evaluate the risk factors for hip fracture among women aged 75 years and older. Over a course of two years (1992- 1994) over 7000 women – free of a previous history of hip fracture or hip replacement – were recruited from five French cities to participate in this study. At baseline evaluation all participants received a full medical examination, which consisted of structured questionnaires, information about everyday dietary habits, chronic diseases, disability, sun exposure and a clinical examination. Medications and vitamin supplements were reported by interviewer questions and also by direct inspection of medications brought to the visit. Women were excluded from the study if over the last 18 months they had taken vitamin D drug supplements. A total of 5,596 women met the inclusion criteria and analyses were based on this sample size.

Dietary habits were assessed at baseline examination using a 21 question food frequency questionnaire that included questions on intake of fish (two items), dairy intake (six items) and the consumption of eggs, fruits, vegetables, starchy foods, chocolate and drinking history. The dietary intake of vitamin D per week was calculated by multiplying the content of individual food items (across all areas) by the frequency of consumption and adding this together. The vitamin D content for all food items was based on a dietary content database – continually updated by the French food and safety agency. For the French adult population, the dietary intake of vitamin D was 400 IU /day (or 35 micrograms/week). The assessment of cognitive function used– the Pfeiffer Short Portable Mental State Questionnaire (SPMSQ). This is a 10 item measure that has been in use in large scale studies as a screening tool to assess moderate to severe cognitive deficits. A score of 8 or below indicates cognitive impairment.

Although the mean weekly dietary intake of vitamin D for the entire group was well above the suggestive value of > 35 micrograms/week (mean 62.3 micrograms/week), approximately 14% of the women had inadequate dietary intakes of vitamin D. Based on the cognitive testing results, a total of 11% of the women were deemed to have cognitive impairment. Further, women who had lower levels of weekly vitamin D intakes had lower mean SPMSQ scores. These women were also older and reported more disability on a disability scale. To further examine the association between weekly vitamin D intake and cognitive function, other factors such as body mass index, sun exposure, number of chronic diseases, history of hypertension, depression, disability or use of antidepressants or other medications, were controlled for in their analyses. The association between dietary vitamin D and cognitive function remained significant even after adjusting for all of these factors.

Although the mean weekly dietary intake of vitamin D for the entire group was well above the suggestive value of > 35 micrograms/week (mean 62.3 micrograms/week), approximately 14% of the women had inadequate dietary intakes of vitamin D. Based on the cognitive testing results, a total of 11% of the women were deemed to have cognitive impairment. Further, women who had lower levels of weekly vitamin D intakes had lower mean SPMSQ scores. These women were also older and reported more disability on a disability scale. To further examine the association between weekly vitamin D intake and cognitive function, other factors such as body mass index, sun exposure, number of chronic diseases, history of hypertension, depression, disability or use of antidepressants or other medications, were controlled for in their analyses. The association between dietary vitamin D and cognitive function remained significant even after adjusting for all of these factors.

This study nicely demonstrates that in women free of vitamin D drug supplementation, weekly dietary intake of vitamin D was significantly associated with the cognitive performance. Few studies have examined the association of dietary vitamin D to cognition in a large population sample. Such studies are needed to clarify whether the associations reported in this study exist in other populations (i.e. U.S. based and those that involve substantial numbers of minority participants) and will guide future research as to whether or not to persue large scale clinical trials that examine the benefits of vitamin D supplementation to treat or prevent cognitive impairment.

Here are 3 articles you can refer to, to learn about this particular study or the latest research on vitamin D and cognitive function:

Dec 152010
 

According to researchers at Columbia University, people with high levels of HDL cholesterol (the “good” form) are 60 percent less likely to develop AD. The researchers followed 1,130 seniors with no history of memory loss or dementia and measured their cholesterol levels every 18 months for four years. When the researchers compared the cholesterol levels of study participants with and without Alzheimer’s, they found that those with the highest HDL counts, greater than 55 mg/dL, had about a 60 percent reduced risk of developing the disease compared to those whose levels were less than 39 mg/dL.

Their findings support the theory that high levels of HDL cholesterol are correlated with lower incidence of AD. The study was published earlier this week in the Archives of Neurology and sheds more light on the interactions between cholesterol and AD.

Apolipoprotein E (apoE), as readers of this blog will recall, participates in the mobilization and distribution of cholesterol among various tissues of the body, including the brain. In humans, there are three common isoforms of apoE: apoE2, apoE3 and apoE4. ApoE4 differs from apoE3, the most common isoform of apoE. A single e4 allele is sufficient to increase the risk of developing atherosclerosis, and also Alzheimer’s disease. The e4 allele results in slightly elevated plasma LDL cholesterol levels and a small but significant decrease in plasma HDL levels. HDL is one of the major carriers of protein in and out of the brain, and also binds to beta-amyloid.

This finding further advances the idea that the interplay between cholesterol, cholesterol-carrying proteins such as apoE and HDL, and beta-amyloid may be critical in the development of Alzheimer’s disease. This study has important strengths. It is a prospective cohort study designed for the diagnosis of cognitive decline that has complete clinical and neuropsychological evaluation at each interval.

Guidelines recommend that men raise HDL levels that are less than 40 mg/dL and that women increase HDL numbers less 50 mg/dL. An HDL of 60 mg/dL or higher is optimal.

Michael S. Rafii, M.D., Ph.D.
Associate Medical Director, ADCS Medical Core
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

* Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease. Christiane Reitz et al., Arch Neurol. 2010;67(12):1491-1497.

Learn More

Nov 022010
 
Confused Lady

Dear Readers,

Whenever I give a presentation about the signs and symptoms of Alzheimer’s disease and discuss the known risk factors for the disease, I am asked this question . . . ( 90% of the time by the women audience members) . . . “Dr. A, is stress a risk factor for Alzheimer’s disease?”

Well, based on research findings from a variety of studies, the short answer is “Yes.” Let’s consider the latest finding from a study that revealed that stress in middle-aged women could lead to the development of dementia later on in life.

This research is based on a 35-year-study of 1,415 women from the Prospective Population Study of Women in Gothenburg, Sweden. The women were initially examined in 1968 (ages ranged from 38 years to 60 years), and then re-examined in the following cycles: 1974, 1980, 1992 and 2000. In addition to neuropsychiatric tests and questions on activities of daily living, the following question was asked by a physician to measure the level of stress in the first three cycles of data collection: “Have you experienced any period of stress (one month or longer) in relation to circumstances or everyday life, such as work, health or family situations?”

The measure of “stress” was defined as a sense of irritation, tension, nervousness, anxiety, fear or sleeping problems. Participants were asked to choose “0″ if they never experienced stress, “1″ if they have experienced stress more than five years ago, “2″ if have experienced one period of stress during the last five years, “3″ if they have experienced several periods of stress during the last five years, “4″ if they have constant stress during the last year, or “5″ if they have experienced constant stress during the last five years.

In addition, data was collected on a variety of factors (i.e. confounders) that may affect the association of stress to dementia, such as lifestyle factors (smoking and wine consumption), coronary heart disease, blood pressure and use of antihypertensive medication.

Participants were classified as having dementia at each cycle if they fulfilled the criteria put forth by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The diagnosis of Alzheimer’s disease was based on criteria put forth by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association. The diagnosis of vascular dementia was based on the criteria proposed by the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et 1″Enseignement en Neurosciences.

Of the women initially assessed in 1968, 161 developed dementia during the follow-up period of 35 years (105 diagnosed with Alzheimer’s disease, 40 diagnosed with vascular dementia, 16 with another type of dementia). The average age of dementia onset was 76 years. Stress that was rated as “frequent/constant” at the baseline and follow up cycles (1968, 1974 and 1980) was related to increased risk of developing dementia and these associations did not change when adjusted for potential confounding variables.

In addition, among women who participated in all three examinations, the risk of dementia increased with the number of examinations when stress was reported. Compared to a woman who never reported stress, if a woman reported stress at one examination cycle her risk for dementia was 1.10, if she reported stress at two examination cycles her risk was 1.73, and if she reported stress at three examination cycles the risk of dementia rose to 2.51.

These findings suggest that long standing psychological stress in middle-aged females is related to the development of dementia later in life. How the present findings could result in a better understanding of the risk factors for dementia and Alzheimer’s disease will need to be confirmed in studies that aim to study the potential neurobiological mechanisms for these associations.

Here are three articles you can refer to, to learn about this particular study or research in the area of Stress and dementia.

Johansson L, Guo X, Waern M et al. Midlife psychological stress and risk of dementia: a 35 year longitudinal population study. Brain,2010.

Hange D, Bengtsson C, Sundh V et al. The natural history of psychosomatic symptoms and their association with psychological symptoms: observations from the Population Study of Women in Gothenburg. Eur J Gen Pract 2007.

Wilson RS, Evans DA, Bienias JL et al. Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology 2003.

Thanks for reading.

Neelum T. Aggarwal, M.D.
Steering Committee Member, ADCS
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

Oct 182010
 

Dear Readers,

Many of our patients and their physicians are aware that physical inactivity and obesity are at epidemic proportions in the United States, which has resulted in an increased prevalence of chronic diseases. Relatively few, however, realize that both these conditions may be associated with poor memory function.

Let’s consider the issue of obesity. Over the years, obesity has truly become a woman’s issue. Sixty five million of the 72 million American adults who are considered obese or overweight are women. In addition African American and Hispanic women are much more likely to be obese than white women. So what does being obese or overweight have to do with cognition in women?

Well, recent findings from the Women’s Health Initiative, suggest that the more an older woman weighs, the poorer her memory will be. In this study, a total of 8,745 cognitively normal, post-menopausal women ages 65 to 79 underwent baseline cognitive testing as part of their routine evaluation. This study used the Modified MMSE examination ( a 100 point memory test) as the measure of cognitive function. The 3MSE has been widely used in large population based studies as a cognitive tool and has demonstrated good consistency, reliability, sensitivity and specificity for detecting cognitive impairment and dementia. For all women, both waist and hip measurements in addition to body mass index ( BMI) calculations were obtained. All the women were classified into BMI categories that corresponded to the standard World Health Organization classifications for normal weight, underweight, overweight and obesity.

The majority of women in this sample ( 86.6% white) were classified as overweight or obese ( 70%). For every one-point increase in a woman’s BMI, her memory score dropped by one point.( p<0.001). These findings were adjusted for age and educational level and remained unchanged after controlling for common chronic conditions such as diabetes, heart disease and stroke.

When the analyses included waist-hip ratio, BMI and 3MSE, the 3MSE scores for women with low waist-hip ratio decreased as the BMI category increased, although this relationship reversed for women with the highest waist-hip ratios. The 3MSE score increased (i.e. better cognition) with increasing BMI in the highest waist-hip ratio category. These results suggest that women who have a “pear shaped” body type (fat deposited around the hips) have poorer cognitive function compared to “apple shaped” body type women (fat deposited around the waist).

One explanation for these findings is that the production of endogenous estrogen (i.e. “natural” estrogen produced by the body) by abdominal adipocytes ( fat cells) may play a protective role for cognitive function and may be less detrimental than fat in other areas. Further research in this area, and whether any notable differences in the strength and nature of these associations across diverse ethnic groups, will need to be explored.

Check out the articles and links below to learn more:

Thanks for reading.

Neelum T. Aggarwal, M.D.
Steering Committee Member, ADCS
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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