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There are two daunting facts about Alzheimer’s disease that cannot be ignored.
First, the number of individuals afflicted with the disease is growing exponentially – currently at 5.4 million Americans – because more people are living longer and age is the number one risk factor.
Second, there is no cure. Despite hundreds of millions of dollars spent on research, 99 percent of all treatment studies in the last 15 years have failed to find significant benefit. These facts create enormous fear about Alzheimer’s disease, not to mention a fair amount of denial of the diagnosis in early stages and fatalism about existing treatments.
The tragedy of Alzheimer’s disease is compounded by its enormous social and economic burden, including rising health care costs and significant caregiver burden, making it one of the costliest and deadly diseases today.
Diagnosis has always been a fundamental challenge, especially in early stages. Whereas we can use blood and tissue samples to diagnose most other diseases, Alzheimer’s disease does not have a sure-fire diagnostic test aside from examination of affected brain tissue, which is not realistic in patients.
We can improve diagnosis by a careful history and examination, neuropsychological testing, and regular follow-up to look for progressive cognitive loss, but too few patients actually receive such comprehensive assessment.
There is good news, however. Ongoing research has led to an increased understanding of how the pathology of Alzheimer’s disease is linked to the extracellular build-up of insoluble beta-amyloid protein in cerebral neuritic plaques and the intracellular build-up of hyperphosporylated tau protein in neurofibrillary tangles.
Being able to detect the elevated presence of these two toxic elements has revolutionized our approaches to diagnosis and treatment. For example, we can now detect the elevated presence of amyloid and tau through a characteristic ratio in cerebrospinal fluid, or in an amyloid or tau-based PET scan. Other biomarkers that can improve accurate diagnosis include disproportionate hippocampal atrophy seen on high resolution MRI scans and bi-hemispheric loss of cerebral metabolism seen on FDG-PET scans.
Currently, the only FDA-approved treatments for Alzheimer’s disease include four cognitive enhancing agents that provide modest symptomatic improvement. The three medications donepezil, rivastigmine and galantamine boost levels of acetylcholine – the key neurotransmitter in the brain for learning and memory. Another medication called memantine reduces the neurodegenerative effects of overactive glutamate activity in the brain.
State-of-the-art therapy combines one of the acetylcholinesterase inhibitors with memantine in hopes of improving symptoms, even though this approach does not appear to slow the actual course of the disease. Based on the amyloid and tau hypothesis, however, numerous experimental agents are being studied to modify the disease itself or at least to mitigate its impact on the brain. One of the most promising is immunotherapy using anti-amyloid antibodies to break up cerebral plaques and tangles. Preliminary data is promising, indicating that the immunotherapy appears able to reduce amyloid plaque burden and possibly slow down cognitive decline.
Despite these advances, a true cure is not yet in reach. One of the major challenges stems from the fact that this disease begins years if not decades before symptoms appear, meaning that the most effective intervention must occur before widespread brain damage is in place. Current research with high-risk families with known Alzheimer’s disease producing genetic mutations will tell us in the next few years whether this early-intervention approach is the key.
In the meantime, we must adhere to several basic principles of care. Early diagnosis via comprehensive assessment with an expert in Alzheimer’s disease is critical. The use of cognitive enhancing medications should be combined with a physically and mentally active lifestyle to boost brain health and overall well-being. Caregivers need education and support to maintain their health and reduce the burden and cost of caregiving. Volunteers are needed for research studies. Excellent care will at least improve the lives of those afflicted with Alzheimer’s disease, even as we continue our search for a cure.
