Alzheimer’s disease (AD) is a chronic degenerative disorder of the brain that primarily afflicts elderly patients, with the National Institutes of Aging (NIA) estimating increases in prevalence to double every five years past age 65. The disease is primarily caused by either sticky plaques formed in between nerve cells (Beta-amyloid) and/or dense fibrils formed within nerve cells (Tau/neurofibrillary tangles). Both of these features contribute to long-term memory loss (dementia), decrease in brain volume (atrophy) and cognitive impairment. Although physicians can diagnose AD with nearly 90% accuracy, the definitive diagnosis is still made in post-mortem autopsy of the brain. Much like lung cancer, AD lacks sensitive diagnostic tests to detect abnormal pathology early.
Treatments and costs of AD
Currently, there are 4.5-5 million cases of AD, which is expected to triple to nearly 15 million cases by 2050. The biggest risk factor of AD is age: one in ten over age 65 and nearly every other person above age 85 are afflicted with AD. Although there is no cure for AD, several compounds have been approved in the last decade to prevent progression of the disease, some with only mild success. These drugs include: Aricept (1996, Pfizer/Esai Co.), Excelon (2000, Novartis), Razadyne (2001, Ortho-McNeil Neurologics) and Namenda (2003, Forest Laboratories). Physicians and researchers agree that although these drugs show mild improvement in halting the progression of the disease, better imaging techniques that more accurately identify an earlier onset of AD are much more helpful in planning effective treatments.
According to a report commissioned by the Alzheimer’s Association, AD costs American businesses nearly $60 billion annually, with half the costs going toward Alzheimer care and the other half representing caregivers’ loss of productivity, replacements, and absenteeism. To care for an AD-afflicted patient costs approximately $42,000 annually in nursing homes, representing average lifetime patient-care costs of $175,000. Since the disease predominantly affects patients well into their retirement years, the time and monetary costs of care-giving have to be shouldered by family members since AD-patients can live up to 10 years after initial diagnosis.
Neuroimaging as a diagnostic tool
The deposition of plaques and tangles within the brain is detrimental to nerve cells because they generate chronic inflammation and consequently lead to degeneration of neurons. However, unlike certain kinds of cancer or heart disease, there are no biomarkers (i.e., cholesterol levels, blood cell counts, etc.) that can be found in blood or cerebrospinal fluid (CSF, which can be taken from the spinal cord) that can effectively predict onset of AD. So, neuroscientists have been turning to imaging techniques to better resolve plaques and tangles within the living brain.
One such technique that has received much attention in the scientific literature is positron emission tomography (PET), which uses a radioactively labeled glucose molecule to see metabolically active areas of the brain. Since the brain uses nearly 50% of the glucose generated after food intake, a region that is highly metabolic, or using glucose to generate the body’s energy compound ATP (adenosine tri-phosphate), is visible as more densely lit structures in PET scans. In 2003, a research team from the University of Pittsburgh reported that, using a tracer (Pittsburgh Compound B, or PIB) that can specifically label amyloid plaques, PET scans show significant amyloid deposits in living subjects with AD.
As the tracer molecules of amyloid, like PIB, get better developed, these compounds can be used with PET scans and full neurological exams to allow clinicians to more accurately diagnose the onset of AD in people who may have family history of AD or show the initial signs of memory loss. Other imaging techniques on the horizon include single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), which are especially useful in visualizing the brains of patients that have various stages of AD. These imaging techniques are also being used in conjunction with drug treatments to identify whether prescribing Alzheimer-specific drugs is beneficial in reducing amyloid deposits in patients.
Future of Neuroimaging
The etiology of AD is being actively pursed from all angles, from genetic factors to clinical hallmarks and molecular mechanisms. The NIA has already started a new Neuroimaging Initiative in October, 2004: a $60 million, 5-year study partnering 50 academic sites to recruit and study AD patients using MRI and PET. The Initiative has also received financial support of $20 million from the pharmaceutical industry, including Pfizer, Merck, Eli Lilly, GlaxoSmithKline, AstraZeneca, Novartis and Wyeth. The breakthroughs of the future will lie in identifying specific molecular tools to visualize initial plaque/tangle formations before the detrimental manifestations of memory loss and neurodegeneration occur. Additionally, advancements in neuroimaging as they pertain to greater spatial resolution and image analysis will undoubtedly bring confidence to physicians as they identify specific treatment programs for their patients.
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