Alzheimer's Club

"WASHINGTON (19 June 2005) -- Advanced imaging technologies and novel biomarkers show great promise for earlier detection of Alzheimer's disease and dementia, as demonstrated by new research studies reported today at the first Alzheimer's Association International Conference on Prevention of Dementia in Washington.

"Earlier identification of Alzheimer's may enable earlier treatment and empower people to plan for their future sooner, including financial and legal matters," said William Thies, Ph.D., vice president, Medical and Scientific Affairs at the Alzheimer's Association. "Yet a large proportion of people with dementia are not diagnosed until the disease is in the moderate or advanced stages. As better treatments and prevention strategies emerge, this situation has to change. The Alzheimer's Association, the National Institute on Aging and industry are pushing hard for earlier detection and earlier intervention."

PET Scans May Predict Alzheimer's In Normal Elderly

Lisa Mosconi, Ph.D., and colleagues at the New York University School of Medicine examined 53 normal elderly subjects (age 67(plus or minus)8 years, range 50-84) who completed a longitudinal study using Positron Emission Tomography (PET) with fluoro-deoxyglucose (FDG) to study brain glucose metabolism. Glucose metabolism is the major energy source of the brain and is a sensitive indicator of brain damage. Subjects were followed for a period ranging from 10 to 24 years and had two or three PET scans. At the end of the study, six subjects had declined to Alzheimer's and 19 showed mild cognitive impairment (MCI).

At baseline of the study, reductions in glucose metabolism in the brain's hippocampus (Hip MRglc) were found for those study participants who would eventually decline to Alzheimer's or MCI, as compared to the non-decliners. Hip MRglc measurements taken at the beginning of the study predicted clinical outcome with a sensitivity of 83 percent for the Alzheimer's cases and 79 percent for the MCI cases. The follow-up Hip MRglc measures yielded equivalent prediction accuracy.

"This is the first brain imaging study to demonstrate detection of sporadic Alzheimer's disease in normal elderly subjects," Mosconi said. "This data suggests that the recognition of future Alzheimer's disease in a person who is cognitively normal is a realistic goal."

MR Spectroscopy May Show Presymptomatic Changes in Alzheimer's

Alison Godbolt of the Dementia Research Centre, Institute of Neurology, University College London, UK, and colleagues agreed with the widely held hypothesis that the biochemical and structural changes in the brain that eventually cause Alzheimer symptoms are actually present before memory loss begins.

To test this theory they examined seven people who were confirmed to have a gene mutation for early onset familial Alzheimer's disease (FAD), but were not yet showing any symptoms, and six healthy comparison subjects without Alzheimer's in the family. All 13 participants had a range of research tests, including MRS (magnetic resonance spectroscopy) brain scans. MRS scans are acquired in the same scanner as an MRI scan, but show levels of brain biochemicals rather than brain structure.

People who have a gene mutation for FAD are almost certain to develop Alzheimer's. The age at which they will develop symptoms can be predicted to some extent from the age at which other members of their family have developed the disease, which is often very similar in all sufferers in the family.

Using MRS, the researchers measured levels of two biochemicals that have previously been found to have altered levels in people with Alzheimer's: N-acetyl aspartate (NAA) and myo-inositol (MI). They measured these biochemicals in a region towards the back of the brain (the posterior cingulate) that is known to be involved in Alzheimer's.

MRS scans revealed different levels of the two brain biochemicals in the participants with the FAD gene mutations, when compared to the other subjects. NAA levels were reduced by statistically significant amounts. A borderline increase in MI levels was seen. The ratio of NAA to MI was reduced by a statistically significant amount. In addition, the size of the changes was related to how close participants were to the age when symptoms were predicted to start.

"Using MRS, we may be able to detect brain biochemical changes in healthy people who will later develop familial Alzheimer's, before their symptoms begin," Godbolt said. "Because this genetic form of Alzheimer's disease is rare and the number of participants in this study is relatively small, our findings must be confirmed with larger studies."

Plasma Beta-amyloid Levels As A Marker for Cognitive Decline, MCI and Alzheimer's

Rather than using advanced imaging technologies to examine the brain, Neill Graff-Radford, MBBCH, FRCP, of the Mayo Clinic Jacksonville, FL and colleagues analyzed plasma for levels of the beta-amyloid protein (AB) to determine if it is useful for identifying individuals at risk for Alzheimer's.

AB is normally present in blood and cerebrospinal fluid. Most AB is composed of 40 amino acids (AB40) but a small percentage has 42 amino acids (AB42). In people with Alzheimer's disease, AB42 forms plaques that are one of the pathological hallmarks of the disease.

The researchers followed 563 normal elderly volunteers (median age 78) for two to 12 years after blood was drawn for analysis of AB42 and AB40. At each visit, cognition was assessed using the Mattis Dementia Rating Scale (DRS), a 144-point cognitive test.

They found that subjects with low plasma AB42/AB40 ratios were at significantly greater risk for developing MCI or Alzheimer's, and they showed significantly greater cognitive decline as measured by the DRS. Subjects with plasma AB42/AB40 ratios in the lowest 25 percent of those studied had a significant three-fold increase in relative risk for MCI or Alzheimer's. Subjects in this group also developed MCI or Alzheimer's first, followed by those in the second 25 percent. MCI or Alzheimer's developed considerably later in subjects whose ratios were in the upper half.

"To develop and administer preventive therapy for Alzheimer's, it is essential to have markers that identify at-risk individuals in the same way that cholesterol levels are used to identify those at risk for heart disease," Graff-Radford said. "Our results indicate that the AB42/AB40 ratio may be a good biomarker for identifying normal elderly who will develop MCI or Alzheimer's in three to five years."

Screening for Dementia In Primary Care Settings

Recognizing that early detection of Alzheimer's disease is a work in progress, Henry Brodaty, AO, MB, BS, MD, FRACP, FRANZCP, Head of the Memory Disorders Clinic, Prince of Wales Hospital, Australia, and colleagues sought to determine the best currently available dementia screening instrument for general practitioners to use now.

"Primary care practitioners are the first port of call for people with progressive cognitive decline, and thus they are best situated to detect dementia early," Brodaty said. "Yet a large proportion of people with dementia are not being diagnosed until their disorder is advanced. One of several reasons cited by general practitioners for their failure to screen is the lengthy nature and inadequacies of current screening tools such as the Mini-mental State Examination (MMSE)."

The researchers located published research on the subject through the major medical databases, with 16 screening instruments included in the final review. They found that few of the screening tests had been tested in primary care or general population samples.

The researchers identified the General Practitioner Assessment of Cognition (GPCOG), Mini-Cog, and Memory Impairment Screen (MIS) were most suitable for routine screening.

"The GPCOG, Mini-Cog, and MIS were all validated in community, population, or general practice samples, are easy to administer, and have administration times under five minutes," Brodaty said. "These instruments have negative predictive validities and misclassification rates at least as good if not better than the MMSE, but are quicker and easier to perform. We recommend that general practitioners adopt routine screening using the GPCOG, Mini-Cog, or MIS when patients are over age 75 or when cognitive impairment is suspected."

How Early Detection Impacts Individuals Being Diagnosed

According to Brodaty, what remains unclear is whether screening for dementia is beneficial. The topic raises many valid questions: Should everyone over a certain age have their cognitive status checked? What are the costs and benefits of earlier diagnoses? Is it ethical to screen for a condition for which we have no cure? What are the ramifications of diagnosing mild cognitive impairment? Is labeling deleterious? Does earlier pharmacotherapy with current medications really make a difference?

To begin to address these questions, Renee Beard, Ph.D., a National Institute on Aging Post-Doctoral Fellow in Gerontological Public Health at the Institute for Health Research and Policy, University of Illinois at Chicago, devoted 18 months to observing the diagnostic process, including observation and qualitative interviews with 50 people undergoing cognitive evaluation and focus groups with 35 individuals diagnosed with Alzheimer's or MCI.

Beard's data suggest that the experience of neuropsychiatric testing involves feelings of embarrassment, confusion, and alienation. Reactions to the diagnosis included shock, sadness, and fear, but also mixed emotions and relief to be able to give a name to their experiences of forgetfulness. After being diagnosed, individuals in the study tried to avoid being seen as defective by others. Strategies included using humor, being proactive, focusing on the positive, accepting help, and admitting their losses.

Diagnosed individuals said that there were positive aspects of being diagnosed, including having the time to plan for the future and focus on what is important to them, along with getting access to resources such as support groups and research studies. People in the study who were diagnosed in the earliest stages of memory loss were able to manage the symptoms of memory loss quite well.

"Although the disease involves many serious problems for diagnosed individuals and their families, Alzheimer's usually progresses slowly and there is typically a substantial time before a person needs assistance," Beard said. "During this period, how others interact with people who have been diagnosed is especially important."

"Early detection of Alzheimer's has granted researchers access to a population of people who are able to articulate their experiences and needs. By understanding the experiences of being tested and living with memory loss, we can significantly improve clinical practice. It is critical to continue exploring the individual, social, and bioethical consequences of increasingly earlier diagnoses," Beard said.

About the Alzheimer's Association

The Alzheimer's Association, the world leader in Alzheimer research and support, is the first and largest voluntary health organization dedicated to finding prevention methods, treatments and an eventual cure for Alzheimer's. For 25 years, the donor-supported, not-for-profit Alzheimer's Association has provided reliable information and care consultation; created supportive services for families; increased funding for dementia research; and influenced public policy changes.

The Alzheimer's Association's vision is a world without Alzheimer's and its dual mission is to eliminate Alzheimer's disease through the advancement of research and to enhance care and support for individuals, their families and caregivers. For more information, call (800) 272-3900 or visit http://www.alz.org/ .

Lisa Mosconi - Hippocampal Metabolism In The Longitudinal Prediction Of Decline From Normal Cognition To MCI And AD (funder: National Institutes of Health/National Institute on Aging) -- Alison Godbolt - MR Spectroscopy Demonstrates Presymptomatic Changes In Familial Alzheimer's Disease (funder: The Medical Research Council, UK) ; Neill Graff-Radford - Plasma AB Levels as a Premorbid Biomarker for Cognitive Decline, Mild Cognitive Impairment (MCI) and Alzheimer Disease (AD) (funders: National Institutes of Health/National Institute on Aging, and the Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program) -- Henry Brodaty - What is the Best Dementia Screening Instrument for General Practitioners to Use? (funder: New South Wales Department of Health) -- Renee Beard - Managing Memory Loss: How Early Detection Impacts Individuals Being Diagnosed (doctoral research)

Alzheimer's Association Contact: Alzheimer's Association media line, +1-312-335-4078,media@alz.org , or Prevention Conference press room, June 18-21,+1-202-745-2170

Source: New Research Studies Bring Early Detection of Alzheimer's Disease Closer to Reality. RedNova.com - Dallas, TX, USA (19 June 2005) [FullText]