Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD)

Honolulu, Hawaii / July 10-15, 2010

New Diagnostic Criteria

Scientists here at the ICAD conference presented draft reports on new diagnostic criteria for cognitive impairment and Alzheimer’s disease (AD), laying out the first proposed changes since 1984. Requested by the US National Institute on Aging and the Alzheimer’s Association, the reports covered diagnosis of AD dementia, mild cognitive impairment due to AD and preclinical AD. The new proposals update the diagnostic criteria to more clearly delineate the different stages of the disease and point out the importance of using AD biomarkers, now in the process of research validation. These biomarkers, which can be assessed using PET, MRI and tests of cerebrospinal fluid (CSF), include beta amyloid pathology, neuronal injury, neuronal dysfunction and neurodegeneration.

“There is increasing evidence of the emerging importance of making a diagnosis for dementia using specific biomarkers—even before any diagnosed symptoms occur,” indicated Dr. Serge Gauthier, Director, Alzheimer’s Disease Research Unit, McGill Centre for Studies in Aging, and Professor of Neurology and Neurosurgery, Psychiatry and Medicine, McGill University, Montreal, Quebec. For the practicing clinician, Dr. Gauthier emphasized the current and future usefulness of biomarkers, core diagnostic criteria such as changes in memory and function, and risk assessment tests. Such diagnostic tools may make it possible in the next few years to prescribe disease-modifying agents based on a patient’s individualized risk profile, Dr. Gauthier explained.

Research and presentations at the ICAD conference also focused on the importance of delaying the progression of mild cognitive impairment (MCI) to AD with early interventions.

In particular risk groups—for instance, those with MCI who suffer from depression who seem to progress faster to AD than those without depressive symptoms—cholinesterase inhibitors (ChEIs) such as donepezil may be particularly beneficial, according to Dr. Sandra Black, Brill Chair in Neurology, University of Toronto, Ontario. She noted that while the weight of scientific evidence indicates that ChEIs are not as valuable in MCI as in mild to moderate AD, recent studies such as those by Lu et al. (Neurology 2009;72(24):2115-21) indicate that these treatments may delay progression of MCI to AD in certain subgroups such as those with depression.

Measuring Early Intervention

Research statistics from the Alzheimer’s Association indicate that the prevalence of dementia will increase 225% from 2010 to 2050. In 2009, 34.4 million people suffered from AD, and the worldwide societal cost for the disease exceeded $422 billion. These statistics underscore the need for early intervention and treatment, because research now indicates that not only does early intervention alleviate patient symptoms and caregiver burden, but also decreases health care costs significantly.

Research from the Dementia Demonstration Project, a project of seven Veterans’ Administration medical centres in the US, indicates that early identification, diagnosis and care of AD patients can decrease average outpatient health care costs by 29% one year after diagnosis. In the study of over 8000 patients, a dementia care team in a primary care clinic in each medical centre administered a brief 3-item memory test to veterans age 70 and older scheduled for a primary care visit. Of 8278 veterans who received the test, 26% failed. Thirty-four per cent of those who failed the test returned for a comprehensive evaluation and 95% of that group were diagnosed with cognitive impairment, including 76% with dementia.

Following evaluation of those diagnosed with dementia, a clinical care team met with the patient and family to review the results, discuss diagnosis and outline treatment recommendations, which were targeted to the severity of the dementia and the needs of each patient and caregiver. Patients diagnosed and treated by the dementia care team saw their average outpatient health care costs decline by $1991 in the year after diagnosis compared to those diagnosed without the services of dementia care specialists; these patients experienced cost declines of $406 a year later.

“Research suggests that when the family of someone who is officially diagnosed with AD becomes educated about the disease, and they work together with medical professionals on a care plan, it can reduce the patients’ difficult behavioural and psychiatric symptoms,” remarked Maria Carrillo, PhD, Senior Director, Medical and Scientific Relations, Alzheimer’s Association. Thorough evaluation and follow-up by a team of clinicians can also reduce caregiver stress, she added.

Delaying the Progression of AD

The usefulness of ChEIs such as donepezil in mild to moderate AD was also discussed at the University of Massachusetts symposium. According to presenters, the benefits of these therapies were documented in the initial clinical trials on the medications. They have also proven to be fairly well tolerated in the elderly population with rates of adverse events ranging from 7% to 8%, according to Dr. Black. “Having practiced for many years prior to and after introduction of these therapies, my clinical experience tells me that patients are not declining at the same rate as they used to without these medications,” she stated.

Yet questions remain about the utility of ChEIs in severe AD. It has been difficult to assess the effects of these medications long-term in AD because of the high dropout rate in open-label extension studies, which are also limited by self-selection bias. “With a disease like AD, it’s difficult to keep patients in a trial for longer than six months because they are in continual decline,” Dr. Black explained. Consequently, clinical trials on ChEIs have tended to be limited to those of six months’ duration, and only a few placebo-controlled studies for periods of more than one year have been completed, she told delegates.

However, recent studies have indicated that patients with severe AD treated with ChEIs show benefits in cognition, memory and executive function. Use of these medications has been associated with significantly slower rates of decline in cognition and overall global function.

While some of the results of long-term studies have been contradictory, the weight of the evidence from studies of up to two years indicates that ChEIs may also delay cognitive and functional decline and progression to neuropsychiatric symptoms by up to one year in AD, Dr. Black commented. “There’s also the potential for symptom stabilization in those in the moderate to severe group—50% of patients have no change or improvement after one year and 35% after two years,” she stated.

Tau Protein: Emerging Target in AD Management

Other new research at the ICAD conference highlighted the promise of experimental immunotherapies that target the tau protein, which is believed responsible for the formation of the neurofibrillary tangles seen in AD. In a pooled exploratory analysis of two small randomized, multicentre, double-blind, placebo-controlled studies, researchers found that bapineuzumab—a medication in phase III testing known to be an antibody to beta amyloid plaques—can also effect levels of the abnormal protein phosphor-tau.

When the researchers looked at results of study 201, which involved 35 patients randomized to bapineuzumab or placebo, they found a trend toward a decrease in CSF phosphor-tau in bapineuzumab-treated subjects compared to those who received placebo. In study 202 involving 11 patients, no significant treatment effects were seen. When the researchers combined data from both studies, they found a statistically significant decrease in phosphor-tau among bapineuzumab-treated patients (P=0.0270).

“Although these are small studies, they are important because higher CSF levels of phosphor-tau are correlated with the size of tissue damage in the brain, faster progression from MCI to AD, a more rapid cognitive decline and higher mortality,” indicated lead researcher Kaj Blennow, PhD, University of Gothenburg, Sweden. “These observations suggest that immunotherapy treatment targeting amyloid may also alter neurodegenerative processes that occur later in the disease.”